Important Safety Information for NovoSeven® RT
WARNING: THROMBOSIS
- Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported
- Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT
- Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis
Warnings and Precautions
- Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance
- Patients with congenital hemophilia receiving concomitant treatment with aPCCs (activated prothrombin complex concentrates), older patients particularly with acquired hemophilia and receiving other hemostatic agents, and patients with a history of cardiac and vascular disease may have an increased risk of developing thrombotic events
- Hypersensitivity reactions, including anaphylaxis, can occur with NovoSeven® RT. Patients with a known hypersensitivity to mouse, hamster, or bovine proteins may be at a higher risk of hypersensitivity reactions. Discontinue infusion and administer appropriate treatment when hypersensitivity reactions occur
- Factor VII deficient patients should be monitored for prothrombin time (PT) and factor VII coagulant activity (FVII:C). If FVII:C fails to reach the expected level, or PT is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed
- Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis
Adverse Reactions
- The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia
Drug Interactions
- Thrombosis may occur if NovoSeven® RT is administered concomitantly with Coagulation Factor XIII
Please click here for NovoSeven® RT Prescribing Information, including Boxed Warning.
Indications and Usage
NovoSeven® RT (coagulation Factor VIIa, recombinant) is a coagulation factor indicated for:
- Treatment of bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets
- Treatment of bleeding episodes and perioperative management in adults with acquired hemophilia
Important Safety Information for Ozempic®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Ozempic® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Ozempic® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Ozempic® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Ozempic®
Contraindications
- Ozempic® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a hypersensitivity reaction to semaglutide or to any of the excipients in Ozempic®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with Ozempic®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Ozempic® and initiate appropriate management
- Diabetic Retinopathy Complications: In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with Ozempic® (3.0%) compared with placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Never Share an Ozempic® Pen Between Patients: Ozempic® pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens
- Hypoglycemia: Patients receiving Ozempic® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Ozempic® that could lead to volume depletion, especially during dosage initiation and escalation
- Severe Gastrointestinal Adverse Reactions: Use of Ozempic® has been associated with gastrointestinal adverse reactions, sometimes severe. In Ozempic® clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Ozempic® (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Ozempic® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with Ozempic®. If hypersensitivity reactions occur, discontinue use of Ozempic®; treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients treated with Ozempic® 0.5 mg and 1 mg, respectively, and not reported in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Ozempic® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Ozempic®
Adverse Reactions
- The most common adverse reactions, reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation
drug-interactions
Drug Interactions
- Updated bullet
- When initiating Ozempic®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- Ozempic® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications, so caution should be exercised
Use in Specific Populations
- There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Discontinue Ozempic® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
Please click here for Ozempic® Prescribing Information, including Boxed Warning.
Indications and Usage
Ozempic® (semaglutide) injection 0.5 mg, 1 mg, or 2 mg is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
- to reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes and established CV disease
- to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Contraindications
- RYBELSUS® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with RYBELSUS®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS®. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back), nausea or vomiting. If pancreatitis is suspected, discontinue RYBELSUS® and initiate appropriate management
- Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials with RYBELSUS®, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with RYBELSUS® and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Hypoglycemia: Patients receiving RYBELSUS® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to RYBELSUS® that could lead to volume depletion, especially during initiation and escalation of RYBELSUS®
- Severe Gastrointestinal Adverse Reactions: Use of RYBELSUS® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving RYBELSUS® (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). RYBELSUS® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with RYBELSUS®. If hypersensitivity reactions occur, discontinue use of RYBELSUS®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials to improve glycemic control, cholelithiasis was reported in 1% of patients treated with RYBELSUS® 7 mg. In a 4-year cardiovascular outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with RYBELSUS® 14 mg and in 0.9% of placebo-treated patients. In Trial 7, cholecystitis was reported in 1.1% treated with RYBELSUS® 14 mg and in 0.7% of placebo-treated patients. If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: RYBELSUS® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking RYBELSUS®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation
Drug Interactions
- RYBELSUS® stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating RYBELSUS®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- RYBELSUS® delays gastric emptying and has the potential to impact the absorption of other oral medications. Closely follow RYBELSUS® administration instructions when coadministering with other oral medications and consider increased monitoring for medications with a narrow therapeutic index, such as levothyroxine
Use in Specific Populations
- Pregnancy: Available data with RYBELSUS® are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue RYBELSUS® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
- Lactation: A clinical lactation study reported semaglutide concentrations below the lower limit of quantification in human breast milk. However, salcaprozate sodium (SNAC) and/or its metabolites are present in human milk. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, an absorption enhancer for RYBELSUS®, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with RYBELSUS®
Please click here for RYBELSUS® Prescribing Information, including Boxed Warning.
Indication and Usage
RYBELSUS® (semaglutide) tablets 7 mg or 14 mg is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events
Important Safety Information for Saxenda®
WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®.
Contraindications
Saxenda® is contraindicated in:
- Patients with a personal or family history of MTC or patients with MEN 2
- Patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in Saxenda®. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Saxenda®
Warnings and Precautions
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back), nausea or vomiting. If pancreatitis is suspected, discontinue Saxenda® and initiate appropriate management
- Acute Gallbladder Disease: Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in patients treated with Saxenda® than with placebo even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Hypoglycemia: Adult patients with type 2 diabetes on an insulin secretagogue (eg, a sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia with use of Saxenda®. The risk may be lowered by a reduction in the dose of insulin secretagogues or insulin. In pediatric patients without type 2 diabetes, hypoglycemia occurred. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms
- Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed in patients treated with Saxenda®. Monitor heart rate at regular intervals and inform patients to report palpitations or feelings of a racing heartbeat while at rest during treatment with Saxenda®. Discontinue Saxenda® in patients who experience a sustained increase in resting heart rate
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury which may sometimes require hemodialysis, in patients treated with liraglutide. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Saxenda® that could lead to volume depletion, especially during initation and escalation of Saxenda®
- Severe Gastrointestinal Adverse Reactions: Use of Saxenda® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Saxenda® (4.8%) than placebo (1.4%). Saxenda® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported in patients treated with Saxenda®. If a hypersensitivity reaction occurs, patients should stop taking Saxenda® and promptly seek medical advice
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Saxenda® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Saxenda®
Adverse Reactions
- The most common adverse reactions, reported in ≥5% are nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia, and gastroenteritis
Drug Interactions
- Saxenda® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. Monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®
Use in Specific Populations
- Saxenda® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- There are no data on the presence of liraglutide in human breast milk; liraglutide was present in the milk of lactating rats
- Saxenda® has not been studied in patients less than 12 years of age
Please click here for Saxenda® Prescribing Information, including Boxed Warning.
Indications and Usage
Saxenda® (liraglutide) injection 3 mg is indicated in combination with reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in:
- Adults and pediatric patients aged 12 years and older with body weight greater than 60kg and obesity
- Adults with overweight in the presence of at least one weight related comorbid condition
Limitations of Use
- Saxenda® contains liraglutide and should not be coadministered with other liraglutide-containing products or with any other GLP-1 receptor agonist
- The safety and effectiveness of Saxenda® in pediatric patients with type 2 diabetes have not been established
Important Safety Information for Vagifem®
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER
Estrogen-Alone Therapy
Endometrial Cancer
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Cardiovascular Disorders and Probable Dementia
The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.
The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.
Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen Plus Progestin Therapy
Cardiovascular Disorders and Probable Dementia
The WHI estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), DVT, stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.
Breast Cancer
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Contraindications
- Undiagnosed abnormal genital bleeding
- Breast cancer or a history of breast cancer
- Estrogen-dependent neoplasia
- Active DVT, PE, or history of these conditions
- Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions
- Known anaphylactic reaction, angioedema, or hypersensitivity to Vagifem®
- Hepatic impairment or disease
- Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Warnings and Precautions
- Risks from systemic absorption: Vagifem® is intended only for vaginal administration. Systemic absorption occurs with the use of Vagifem®. The warnings, precautions, and adverse reactions associated with the use of systemic estrogen-alone therapy should be taken into account.
- Cardiovascular Disorders: Immediately discontinue estrogen with or without progestogen therapy if PE, DVT, stroke, or MI occur or are suspected.
- Malignant Neoplasms: Extension of the WHI trials also demonstrated increased breast cancer risk associated with systemic estrogen plus progestin therapy. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use of systemic estrogen plus progestin therapy and systemic estrogen-alone therapy. These risks could last up to >10 years after discontinuation of these systemic therapies depending on the duration of use. There was no increase in risk of developing breast cancer in women taking vaginal estrogens. The CE plus MPA substudy of WHI reported a statistically non-significant increased risk of ovarian cancer with the use of estrogen plus progestin. A meta-analysis of 17 prospective and 35 retrospective studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer.
- Gallbladder disease: A 2-4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
- Discontinue Vagifem® if severe hypercalcemia, visual abnormalities (sudden loss of vision, sudden onset of proptosis, diplopia, or migraine), severe hypertriglyceridemia, cholestatic jaundice or medically concerning fluid retention occurs.
- Exacerbation of Hypothyroidism: Monitor thyroid function in women on thyroid hormone replacement therapy who are also receiving estrogens because estrogen leads to increased thyroid-binding globulin (TBG) levels.
- Local abrasion: A few cases of local abrasion induced by the Vagifem® applicator have been reported.
Adverse Reactions
- The most common adverse reactions (incidence ≥5 percent) with Vagifem® are back pain, vulvovaginal pruritus, vulvovaginal mycotic infection, and diarrhea.
Drug Interactions
- Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
Please click here for Vagifem® Prescribing Information, including Boxed Warning.
Important Safety Information for Victoza®
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined
- Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Victoza® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza®
Contraindications
- Victoza® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in Victoza®. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Victoza®
Warnings and Precautions
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated
- Acute Pancreatitis: Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including Victoza®. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain, (sometimes radiating to the back), nausea, or vomiting. If pancreatitis is suspected, discontinue Victoza® and initiate appropriate management
- Never Share a Victoza® Pen Between Patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens
- Hypoglycemia: Adult patients receiving Victoza® in combination with an insulin secretagogue (eg, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher with Victoza® regardless of insulin and/or metformin use
- Acute Kidney Injury Due to Volume Depletion : There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with Victoza®. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Victoza® that could lead to volume depletion, especially during dosage initiation and escalation of Victoza®
- Severe Gastrointestinal Adverse Reactions: Use of GLP-1 receptor agonists, including Victoza®, has been associated with gastrointestinal adverse reactions, sometimes severe. In Victoza® clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Victoza® (1.2 mg 4.4 %, 1.8 mg 4.2 %) than placebo (1.1 %). Victoza® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with Victoza®. If a hypersensitivity reaction occurs, discontinue Victoza®; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity reaction to Victoza®. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Victoza®
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In the LEADER trial, 3.1% of Victoza®-treated patients versus 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Victoza® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Victoza®
Adverse Reactions
- The most common adverse reactions (incidence ≥5%) in clinical trials are nausea, diarrhea, vomiting, decreased appetite, dyspepsia, and constipation
- Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials
Drug Interactions
- Victoza® delays gastric emptying and may impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with Victoza®
- When initiating Victoza®, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
Use in Specific Populations
- Victoza® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- The safety and effectiveness of Victoza® have not been established in pediatric patients less than 10 years of age
Please click here for Victoza® Prescribing Information, including Boxed Warning.
Indications and Limitations of Use
Victoza® (liraglutide) injection 1.2 mg or 1.8 mg is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes and established cardiovascular disease.
- Victoza® contains liraglutide and should not be coadministered with other liraglutide-containing products
Important Safety Information for Wegovy®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Wegovy® is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Wegovy® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Wegovy®
Contraindications
- Wegovy® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in Wegovy®. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with Wegovy®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including Wegovy®. Observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent severe abdominal pain (sometimes radiating to the back), nausea, or vomiting. If acute pancreatitis is suspected, discontinue Wegovy® and initiate appropriate management
- Acute Gallbladder Disease: Treatment with Wegovy® is associated with an increased occurrence of cholelithiasis and cholecystitis. The incidence of cholelithiasis and cholecystitis was higher in Wegovy® pediatric patients aged 12 years and older than in Wegovy® adults. In clinical trials in adult patients for weight reduction, cholelithiasis was reported by 1.6% of Wegovy® patients and 0.7% of placebo patients. Cholecystitis was reported by 0.6% of Wegovy® patients and 0.2% of placebo patients. In a clinical trial in pediatric patients aged 12 years and older for weight reduction, cholelithiasis was reported by 3.8% of Wegovy® patients and 0% placebo patients. Cholecystitis was reported by 0.8% of Wegovy® pediatric patients and 0% placebo patients. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Wegovy® patients than in placebo patients, even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Hypoglycemia: Wegovy® lowers blood glucose and can cause hypoglycemia. In a trial of adult patients with type 2 diabetes for weight reduction, hypoglycemia was reported in 6.2% of Wegovy® patients versus 2.5% of placebo patients. Patients with diabetes taking Wegovy® with an insulin or insulin secretagogue (e.g. sulfonylurea) may have an increased risk of hypoglycemia, including severe hypoglycemia. The use of Wegovy® in patients with type 1 diabetes or in combination with insulin has not been evaluated. Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms. Monitor blood glucose in patients with diabetes
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Wegovy® that could lead to volume depletion, especially during initiation and escalation of Wegovy®
- Severe Gastrointestinal Adverse Reactions: Use of Wegovy® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials in adults for weight reduction, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Wegovy® (4.1%) than placebo (0.9%). Wegovy® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with Wegovy®. If hypersensitivity reactions occur, discontinue use of Wegovy®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist
- Diabetic Retinopathy Complications in Patients with Type 2 Diabetes: In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m2 for weight reduction, diabetic retinopathy was reported by 4.0% of Wegovy® patients and 2.7% of placebo patients. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy
- Heart Rate Increase: Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed in Wegovy® adult patients compared to placebo in weight reduction clinical trials. More Wegovy® adult patients compared with placebo had maximum changes from baseline of 10 to 19 bpm (41% versus 34%) and 20 bpm or more (26% versus 16%). In a clinical trial for weight reduction in pediatric patients aged 12 years and older with normal baseline heart rate, more patients treated with Wegovy® compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%). Monitor heart rate at regular intervals and instruct patients to report palpitations or feelings of a racing heartbeat while at rest. If patients experience a sustained increase in resting heart rate, discontinue Wegovy®
- Suicidal Behavior and Ideation: Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients for depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Wegovy® in patients who experience suicidal thoughts or behaviors and avoid in patients with a history of suicidal attempts or active suicidal ideation
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Wegovy® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Wegovy®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distention, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis
Drug Interactions
- The addition of Wegovy® in patients treated with insulin has not been evaluated. When initiating Wegovy®, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- Wegovy® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. Monitor the effects of oral medications concomitantly administered with Wegovy®
Use in Specific Populations
- Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Wegovy®. Discontinue Wegovy® in patients at least 2 months before a planned pregnancy
- Pediatric: Adverse reactions with Wegovy® in pediatric patients aged 12 years and older with obesity were similar to those reported in adults in weight reduction trials. Pediatric patients ≥12 years of age treated with Wegovy® had greater incidences of cholelithiasis, cholecystitis, hypotension, rash, and urticaria compared to adults treated with Wegovy®. There are insufficient data in pediatric patients with type 2 diabetes treated with Wegovy® for obesity to determine if there is an increased risk of hypoglycemia with Wegovy® treatment similar to that reported in adults
- Geriatric: In the cardiovascular outcomes trial, patients aged 75 years and older reported more hip and pelvis fractures on Wegovy® than placebo. Patients aged 75 years and older (Wegovy® and placebo) reported more serious adverse reactions overall compared to younger adult patients
Please click here for Wegovy® Prescribing Information, including Boxed Warning.
Indications and Usage
Wegovy® (semaglutide) injection 2.4 mg is indicated in combination with a reduced calorie diet and increased physical activity:
- for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults.
The indication for MASH is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight
- to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and adults with overweight in the presence of at least one weight-related comorbidity
Limitations of Use:
Wegovy® contains semaglutide. Coadministration with other semaglutide-containing products or with any GLP-1 receptor agonist is not recommended
Important Safety Information for Xultophy® 100/3.6
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide, one of the components of Xultophy® 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy® 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
- Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Xultophy® 100/3.6 and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy® 100/3.6.
CONTRAINDICATIONS
- Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), during episodes of hypoglycemia, and in patients with hypersensitivity to Xultophy® 100/3.6, either of the active substances, or any of its excipients. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of Xultophy® 100/3.6.
WARNINGS AND PRECAUTIONS
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated.
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide, one of the components of Xultophy® 100/3.6. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) nausea or vomiting. If pancreatitis is suspected, discontinue Xultophy® 100/3.6 and initiate appropriate management.
- Never Share a Xultophy® 100/3.6 Pen Between Patients, even if the needle is changed. Sharing of the pen poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Overdose Due to Medication Errors: Instruct patients to check the label before each injection since accidental mix-ups with insulin containing products can occur. Do not administer more than 50 units of Xultophy® 100/3.6 daily. Do not exceed the 1.8 mg maximum recommended dose of liraglutide or use with other GLP-1 RAs.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin-containing products, including Xultophy® 100/3.6. Severe hypoglycemia can cause seizures, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time which may place the patient and others at risk in situations where these abilities are important. Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, diabetic neuropathy, and in patients using drugs that block the sympathetic nervous system, or who experience recurrent hypoglycemia. The long-acting effect of insulin degludec may delay recovery from hypoglycemia compared to shorter acting insulins. Increase monitoring with changes to: dose, co-administered glucose lowering medications, concomitant drugs, meal pattern, physical activity; and in patients with hypoglycemia unawareness or renal or hepatic impairment.
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with liraglutide, one of the components of Xultophy® 100/3.6. The majority of reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting or diarrhea. Monitor renal function in patients reporting adverse reactions to Xultophy® 100/3.6 that could lead to volume depletion, especially during initiation and escalation of Xultophy® 100/3.6.
- Severe Gastrointestinal Adverse Reactions: Use of GLP-1 receptor agonists, including liraglutide, one of the components of Xultophy® 100/3.6, has been associated with gastrointestinal adverse reactions, sometimes severe. In a Xultophy® 100/3.6 clinical trial severe gastrointestinal adverse reactions were reported among patients receiving Xultophy® 100/3.6 (0.8 %) and patients receiving the active comparators liraglutide (2.9%) and insulin degludec (0.2%). Xultophy® 100/3.6 is not recommended in patients with severe gastroparesis.
- Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock can occur with insulins, including Xultophy® 100/3.6. There have been postmarketing reports of serious hypersensitivity reactions (e.g. anaphylactic reactions and angioedema) in patients treated with liraglutide, one of the components of Xultophy® 100/3.6. If a hypersensitivity reaction occurs, discontinue and treat promptly per standard of care, and monitor until signs and symptoms resolve. Anaphylaxis and angioedema have been reported with other GLP-1 RAs. Use caution in a patient with a history of anaphylaxis or angioedema with other GLP-1 RAs because it is unknown whether such patients will be predisposed to these reactions with Xultophy® 100/3.6.
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a cardiovascular outcomes trial (LEADER trial) 3.1% of patients treated with liraglutide, one of the components of Xultophy® 100/3.6, versus 1.9% of placebo treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
- Hypokalemia: All insulin containing products, including Xultophy® 100/3.6 can lead to life-threatening hypokalemia, which may then cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Congestive Heart Failure: Patients using insulin containing products, including Xultophy® 100/3.6, with thiazolidinediones (TZDs) should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Xultophy® 100/3.6 delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Xultophy® 100/3.6.
ADVERSE REACTIONS
- The most common adverse reactions, reported in ≥5% of patients treated with Xultophy® 100/3.6 are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection.
DRUG INTERACTIONS
- Certain drugs may affect glucose metabolism, requiring dose adjustment and close monitoring of blood glucose. The signs and symptoms of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine).
- Liraglutide-containing products, including Xultophy® 100/3.6, cause a delay of gastric emptying, and thereby have the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with liraglutide-containing products.
USE IN SPECIFIC POPULATIONS
- Xultophy® 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Please click here for Xultophy® 100/3.6 Prescribing Information, including Boxed Warning.
Indications and Limitations of Use
Xultophy® 100/3.6 (insulin degludec and liraglutide) injection 100 units/mL and 3.6 mg/mL is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Xultophy® 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist (GLP-1 RA).
- Xultophy® 100/3.6 is not recommended for the treatment of diabetic ketoacidosis.
- Xultophy® 100/3.6 has not been studied in combination with prandial insulin.
Important Safety Information for Alhemo®
Contraindications
- Alhemo® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo® or its ingredients
Warnings and Precautions
- Thromboembolic Events (TEs): Venous and arterial TEs were reported in 1.9% of patients (6/320) who also had multiple risk factors, including the use of high doses or prolonged treatment with factor product or bypassing agent (2 of 6 patients). Risk factors for TEs may also include conditions in which tissue factor is overexpressed (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia). Inform patients about and monitor them for signs and symptoms of TEs. In case of suspicion of TEs, discontinue Alhemo® and initiate further investigations and management strategies
- Hypersensitivity Reactions: Alhemo® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo® or its ingredients. Hypersensitivity reactions, including erythema, rash, pruritus, and abdominal pain, have occurred in patients treated with Alhemo®. One patient (<1%) experienced anaphylaxis, which resolved after treatment with antihistamines and corticosteroids. Instruct patients of the signs of acute hypersensitivity reactions and to contact their healthcare provider for mild reactions and to seek urgent medical attention for moderate to severe reactions. Discontinue Alhemo® if severe hypersensitivity symptoms occur and initiate medical management
- Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2: Increased levels of fibrin D-dimer and prothrombin fragment 1.2 were seen in 29 (9.1%) and 26 (8.1%) patients, respectively, which is positively correlated with the plasma concentration of concizumab-mtci, indicating a hemostatic effect. For patients taking Alhemo®, these coagulation biomarkers may not be reliable predictive markers for clinical decision-making with suspicion of thrombosis, such as deep vein thrombosis and pulmonary embolism
Adverse Reactions
- The most frequently reported adverse reactions (≥5%) were injection site reactions, headache, and urticaria
- Serious adverse reactions were reported in 6.1% of patients with inhibitors who received Alhemo®. Permanent discontinuation of Alhemo® occurred in 1 patient due to a renal infarct and dosage interruptions of Alhemo® occurred in 1 patient (3%) and was a hypersensitivity reaction
Drug Interactions
- Breakthrough Bleeding Treatment: Take appropriate precautions when treating breakthrough bleeding events in patients receiving Alhemo® prophylaxis and FVIII or FIX or a bypassing agent (eg, rFVIIa or aPCC). For mild and moderate bleeds, the lowest approved dose in the approved product labeling is recommended. For aPCC, a maximum dose of 100 units/kg within 24 hours is recommended. For severe bleeds, follow the dosing instructions in the approved labeling based on clinical judgment
Please click here for Alhemo® Prescribing Information.
Indications and Usage
Alhemo® (concizumab-mtci) injection 60 mg, 150 mg, or 300 mg is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or B with or without Factor VIII or IX inhibitors.
Important Safety Information for Esperoct®
Contraindications
- Do not use in patients who have known hypersensitivity to Esperoct® or its components, including hamster proteins
Warnings and Precautions
- Hypersensitivity reactions, including anaphylaxis, may occur. Should hypersensitivity reactions occur, discontinue Esperoct® and administer appropriate treatment
- Development of neutralizing antibodies (inhibitors) has occurred. Perform an assay that measures Factor VIII inhibitor concentration if bleeding is not controlled with the recommended dose of Esperoct® or if the expected plasma Factor VIII activity levels are not attained
- Temporary decrease in Factor VIII incremental recovery (IR) has been observed after Esperoct® infusion, within the first 5 exposure days, in previously untreated patients (PUPs) <6 years of age. During the decreased IR period, these subjects may have an increased bleeding tendency. If bleeding is not controlled with the recommended dose of Esperoct® and/or the expected Factor VIII activity levels are not attained and Factor VIII inhibitors are not detected, consider adjusting the dose, dosing frequency, or discontinuing Esperoct®
Adverse Reactions
- The most frequently reported adverse reactions in clinical trials (≥1%) were rash, redness, itching (pruritus), and injection site reactions. Additional frequently reported adverse reactions (≥1%) in PUPs included Factor VIII inhibition and hypersensitivity.
Please click here for Esperoct® Prescribing Information.
Indications and Usage
Esperoct® [antihemophilic factor (recombinant), glycopegylated-exei] is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes
- Esperoct® is not indicated for the treatment of von Willebrand disease
Important Safety Information for Fiasp®
Contraindications
- Fiasp® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Fiasp® or one of its excipients.
Warnings and Precautions
- Never share a Fiasp® FlexTouch® Pen, PenFill® cartridge or PenFill® cartridge device between patients, even if the needle is changed. Patients using Fiasp® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia is the most common adverse reaction of insulin, including Fiasp®, and may be life-threatening. Increase glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness.
- To avoid medication errors and accidental mix-ups between Fiasp® and other insulin products, instruct patients to always check the insulin label before injection.
- As with all insulins, Fiasp® use can lead to life-threatening hypokalemia, which then may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including Fiasp®.
- Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Fiasp®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
- Pump or infusion set malfunctions can lead to a rapid onset of hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim therapy with subcutaneous injection of Fiasp® may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.
Drug Interactions
- Drugs That May Increase the Risk of Hypoglycemia: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Dose reductions and increased frequency of glucose monitoring may be required.
- Drugs That May Decrease the Blood Glucose Lowering Effect of Fiasp®: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Dose increases and increased frequency of glucose monitoring may be required.
- Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Fiasp®: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required.
- Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Beta-blockers, clonidine, guanethidine, and reserpine. Increased frequency of glucose monitoring may be required
Adverse Reactions
- Adverse reactions observed with Fiasp® include hypoglycemia, allergic reactions, hypersensitivity, injection site reactions, lipodystrophy, and weight gain.
Use in Specific Populations
- Pediatric patients with type 1 diabetes treated with mealtime and postmeal Fiasp® reported a higher rate of blood glucose confirmed hypoglycemic episodes compared to patients treated with NovoLog® (insulin aspart) injection; the imbalance was greater during the nocturnal period. Monitor blood glucose levels closely in pediatric patients.
- Like all insulins, Fiasp® requirements may be reduced in patients with renal impairment or hepatic impairment. These patients may require more frequent blood glucose monitoring and dose adjustments.
Please click here for Fiasp® Prescribing Information.
Important Safety Information for GlucaGen®
Contraindications
GlucaGen® is contraindicated in patients with:
- Pheochromocytoma because of the risk of substantial increase in blood pressure
- Insulinoma because of the risk of hypoglycemia
- Known hypersensitivity to glucagon or the excipients in GlucaGen®. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension
- Glucagonoma when used as a diagnostic aid because of risk of hypoglycemia
Warnings and Precautions
- Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: GlucaGen® is contraindicated in patients with pheochromocytoma because GlucaGen® may stimulate the release of catecholamines from the tumor.
- Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, GlucaGen® administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GlucaGen® is contraindicated in patients with insulinoma. If a patient develops symptoms of hypoglycemia after a dose of GlucaGen®, give glucose orally or intravenously.
- Hypersensitivity and Allergic Reactions: Allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. GlucaGen® is contraindicated in patients with a prior hypersensitivity reaction.
- Lack of Efficacy in Patients with Decreased Hepatic Glycogen: GlucaGen® is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for GlucaGen® administration to be effective. Patients with these conditions should be treated with glucose.
- Necrolytic Migratory Erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, has been reported post-marketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.
- Hyperglycemia in Patients with Diabetes Mellitus when Used as a Diagnostic Aid: Treatment with GlucaGen® in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated.
- Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease when used as a Diagnostic Aid: GlucaGen® may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease. Cardiac monitoring is recommended in patients with cardiac disease during use of GlucaGen® as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy.
- Hypoglycemia in Patients with Glucagonoma: Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. Test patients suspected of having glucagonoma for blood levels of glucagon prior to use as a diagnostic aid as GlucaGen® is contraindicated in this setting.
Adverse Reactions
- Glucagon adverse reactions identified during post approval use are: injection site reactions, nausea, vomiting, headache, dizziness, asthenia, pallor, diarrhea, somnolence, and decreased blood pressure.
Drug Interactions
- Beta-blockers patients taking beta-blockers may have a transient increase in pulse and blood pressure.
- Indomethacin: In patients taking indomethacin, GlucaGen® may lose its ability to raise blood glucose or may produce hypoglycemia.
- Anticholinergic Drugs: Concomitant use of anticholinergic drugs with GlucaGen® for use as a diagnostic aid is not recommended.
- Warfarin: GlucaGen® may increase the anticoagulant effect of warfarin.
- Insulin: Monitor blood glucose when GlucaGen® is used as a diagnostic aid in patients receiving insulin.
Please click here for GlucaGen® Prescribing Information.
Indications and Usage
GlucaGen® (glucagon) for injection 1mg/mL is an antihypoglycemic agent and a gastrointestinal motility inhibitor indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes and as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.
Important Safety Information for Levemir®
Contraindications
- Levemir® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to insulin detemir or any of the excipients in Levemir®. Reactions have included anaphylaxis.
Warnings and Precautions
- Never Share a Levemir® FlexPen® prefilled pen, Needle, or Syringe Between Patients: Levemir® FlexPen® prefilled pens must never be shared between patients, even if the needle is changed. Patients using Levemir® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Levemir®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers), or who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Levemir® may vary among different patients or at different times in the same patient and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. When a GLP-1 receptor agonist is used in combination with Levemir®, the Levemir® dose may need to be lowered or more conservatively titrated to minimize the risk of hypoglycemia. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Levemir® and other insulins, instruct patients to always check the insulin label before each injection.
- Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin, including Levemir®. If hypersensitivity reactions occur, discontinue Levemir®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Levemir®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Levemir®, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.
Adverse Reactions
- Adverse reactions associated with Levemir® include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, rash, and pruritus.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Levemir®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Use in Specific Populations
- Pregnancy: Available data from published studies and postmarketing case reports with Levemir® use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
- Clinical Considerations - Disease-Associated Maternal and/or Embryo/Fetal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
- Clinical Considerations - Disease-Associated Maternal and/or Embryo/Fetal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
Please click here for Levemir® Prescribing Information.
Important Safety Information for Norditropin®
Contraindications
Norditropin® is contraindicated in patients with:
- Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin
- Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death
- Active Malignancy
- Hypersensitivity to Norditropin® or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins
- Active proliferative or severe non-proliferative diabetic retinopathy
- Pediatric patients with closed epiphyses
Warnings and Precautions
- Increased mortality in patients with acute critical illness due to complications following open heart or abdominal surgery or multiple accidental trauma, or those with respiratory failure has been reported.
- Sudden death in pediatric patients with Prader-Willi Syndrome has been reported after initiating treatment with somatropin with one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Evaluate patients for signs of upper airway obstruction and sleep apnea before initiation of treatment.
- Increased risk of neoplasms: Monitor patients with preexisting tumors for progression or recurrence. In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm, in particular meningiomas, has been reported. Pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients carefully for increased growth, or potential malignant changes of preexisting nevi.
- Glucose intolerance and diabetes mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New-onset type 2 diabetes mellitus has been reported. Monitor glucose levels in all patients. Doses of concurrent antidiabetic drugs may require adjustment.
- Intracranial hypertension has been reported in a small number of patients, usually within the first 8 weeks of somatropin treatment. Funduscopic examination should be performed before initiating treatment and periodically thereafter.
- Severe hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins.
- Fluid retention in adults (clinically manifesting as edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) may frequently occur and is usually transient and dose dependent.
- Hypoadrenalism: Patients who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Norditropin® treatment.
- Hypothyroidism if undiagnosed/untreated, may prevent an optimal response to Norditropin®, in particular, the growth response in pediatric patients. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted when indicated.
- Slipped capital femoral epiphysis in pediatric patients may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin, including Norditropin®. Evaluate pediatric patients receiving Norditropin® with the onset of a limp or complaints of hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly.
- Progression of preexisting scoliosis in pediatric patients can occur in patients who experience rapid growth. Patients with a history of scoliosis should be monitored for progression.
- Pancreatitis: Cases of pancreatitis have been reported. Pancreatitis should be considered in any patient who develops persistent severe abdominal pain.
- Lipoatrophy: Tissue atrophy may result when somatropin is administered subcutaneously at the same site over a long period of time. Rotate injection sites when administering Norditropin® to reduce this risk.
Adverse Reactions
- Common adverse reactions in adults and pediatric patients include: upper respiratory infection, fever, pharyngitis, headache, otitis media, edema, arthralgia, paresthesia, myalgia, peripheral edema, flu syndrome, and impaired glucose tolerance
Drug Interactions
- Glucocorticoids: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Norditropin®
- Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatment to avoid both hypoadrenalism and an inhibitory effect on growth
- Cytochrome P450-Metabolized Drugs: Norditropin® may alter the clearance. Monitor carefully if used with Norditropin®
- Oral Estrogen: Larger doses of Norditropin® may be required
- Insulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required
Use in Specific Populations
- Pregnancy and Nursing Mothers: There are limited data with somatropin use in pregnant women and nursing mothers to inform a drug-associated risk for adverse developmental outcomes
- Geriatric Use: The safety and effectiveness in patients aged 65 and over has not been evaluated in clinical studies
Please click here for Norditropin® Prescribing Information.
Indications and Usage
Norditropin® (somatropin) injection 5 mg, 10 mg, or 15 mg is indicated for the treatment of pediatric patients with:
- growth failure due to inadequate secretion of endogenous growth hormone (GH)
- short stature associated with Noonan syndrome
- short stature associated with Turner syndrome
- short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years of age
- Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range
- growth failure due to Prader-Willi syndrome (PWS)
Norditropin® is also indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)
Important Safety Information for Novoeight®
Contraindications
- Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to Novoeight® or its components, including hamster proteins
Warnings and Precautions
- Anaphylaxis and severe hypersensitivity reactions are possible. Patients may develop hypersensitivity to hamster proteins, which are present in trace amounts in the product. Should symptoms occur, discontinue Novoeight® and administer appropriate treatment
- Development of activity-neutralizing antibodies (inhibitors) may occur. Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all factor VIII products. Inhibitors have been reported following administration of Novoeight® in PUPs. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform testing for factor VIII inhibitors
Adverse Reactions
- The most frequently reported adverse reactions (≥1%) were inhibitors in Previously Untreated Patients (PUPs), injection site reactions, and pyrexia.
Please click here for Novoeight® Prescribing Information.
Indications and Usage
Novoeight® (antihemophilic factor, recombinant) is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to reduce the frequency of bleeding episodes.
- Novoeight® is not indicated for the treatment of von Willebrand disease
Important Safety Information for NovoLog®
Contraindications
- NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients.
Warnings and Precautions
- Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse effect of all insulins, including NovoLog®. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers), or in patients who experience recurrent hypoglycemia.
- Risk Factors for Hypoglycemia: The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of NovoLog® may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to co-administered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia.
- Hypoglycemia Due to Medication Errors: To avoid medication errors and accidental mix-ups between NovoLog® and other insulin products, instruct patients to always check the insulin label before injection.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog®.
- Hypokalemia: All insulins, including NovoLog®, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
- Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.
NovoLog® continuous subcutaneous infusion route (insulin pump): Do not mix NovoLog® with any other insulin or diluent.
Adverse Reactions
- Adverse reactions observed with NovoLog® include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus.
Drug Interactions
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine.
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.
Please click here for NovoLog® Prescribing Information.
Important Safety Information for NovoLog® Mix 70/30
Contraindications
- NovoLog® Mix 70/30 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® Mix 70/30 or one of its excipients.
Warnings and Precautions
- Never Share a NovoLog® Mix 70/30 FlexPen®, Needle, or Syringe Between Patients, even if the needle is changed. Patients using NovoLog® Mix 70/30 vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse effect of all insulins, including NovoLog® Mix 70/30. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers), or in patients who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia: The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of NovoLog® Mix 70/30 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to co-administered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. - Hypoglycemia Due to Medication Errors: To avoid medication errors and accidental mix-ups between NovoLog® Mix 70/30 and other insulins, instruct patients to always check the insulin label before injection.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulins, including NovoLog® Mix 70/30. If hypersensitivity reactions occur, discontinue NovoLog® Mix 70/30; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including NovoLog® Mix 70/30, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog® Mix 70/30. Patients should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus.
Use in Specific Populations
- The safety and effectiveness of NovoLog® Mix 70/30 have not been established in pediatric patients. Clinical studies of NovoLog® Mix 70/30 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Drug Interactions
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine.
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.
Please click here for NovoLog® Mix 70/30 Prescribing Information.
Indications and Usage
- NovoLog® Mix 70/30 (insulin aspart protamine and insulin aspart) injectable suspension 100 U/mL is a mixture of insulin aspart protamine and insulin aspart indicated to improve glycemic control in adult patients with diabetes mellitus.
Important Limitations of Use
- NovoLog® Mix 70/30 is not recommended for the treatment of diabetic ketoacidosis.
- The proportions of rapid-acting and long-acting insulins are fixed and do not allow for basal versus prandial dose adjustments.
Important Safety Information for Rebinyn®
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
- Inhibitors: The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following Rebinyn®. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
- Thrombotic Events: The use of Factor IX-containing products has been associated with thromboembolic complications. Monitor for thrombotic and consumptive coagulopathy when administering Rebinyn® to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC).
- Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using Rebinyn® for immune tolerance induction have not been established.
Adverse Reactions
- The most common adverse reactions reported in previously treated patients in clinical trials (≥1%) were itching and injection site reactions. The most common adverse reactions (≥1%) in previously untreated patients reported in clinical trials were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction.
- Animals administered Rebinyn® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. Consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired.
Please click here for Rebinyn® Prescribing Information.
Indications and Usage
Rebinyn®, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for on demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.
Limitations of Use: Rebinyn® is not indicated for immune tolerance induction in patients with hemophilia B.
Important Safety Information for Rivfloza®
Adverse Reactions
Most common adverse reactions (reported in ≥20% of patients) are injection site reactions, which include erythema, pain, bruising, and rash.
Please click here for Rivfloza® Prescribing Information.
Important Safety Information for Sogroya®
Contraindications
Sogroya® is contraindicated in patients with:
- acute critical illness after open-heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure because of the risk of increased mortality with use of Sogroya®
- hypersensitivity to Sogroya® or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with somatropin
- pediatric patients with closed epiphyses
- active malignancy
- active proliferative or severe non-proliferative diabetic retinopathy
- pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to risk of sudden death
Warnings & Precautions
- Increased Mortality in Patients with Acute Critical Illness: Increased mortality has been reported after treatment with somatropin in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery, multiple accidental trauma, and in patients with acute respiratory failure
- Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported postmarketing with use of somatropin. Inform patients and/or caregivers that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs
- Increased Risk of Neoplasms: There is an increased risk of malignancy progression with somatropin in patients with active malignancy. Any preexisting malignancy should be inactive, and its treatment complete prior to instituting Sogroya®. In childhood cancer survivors treated with radiation to the brain/head for their first neoplasm who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Monitor patients with a history of GHD secondary to an intracranial neoplasm for progression or recurrence of the tumor. Children with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients for increased growth or potential malignant changes of preexisting nevi. Advise patients/caregivers to report changes in the appearance of preexisting nevi
- Glucose Intolerance and Diabetes Mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes has been reported. Monitor glucose levels in all patients, especially in those with existing diabetes mellitus or with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The doses of antidiabetic agents may require adjustment when Sogroya® is initiated
- Intracranial Hypertension: Has been reported usually within 8 weeks of treatment initiation. Perform fundoscopic examination prior to initiation of treatment and periodically thereafter. If papilledema is identified, evaluate the etiology, and treat the underlying cause before initiating Sogroya®. If papilledema is observed, stop treatment. If intracranial hypertension is confirmed, Sogroya® can be restarted at a lower dose after intracranial hypertension signs and symptoms have resolved
- Fluid Retention: Was observed during Sogroya® therapy. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes, including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent
- Hypoadrenalism: Patients receiving somatropin therapy who have or are at risk for corticotropin deficiency may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Sogroya®. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases
- Hypothyroidism: Undiagnosed/untreated hypothyroidism may prevent an optimal response to Sogroya®. Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of Sogroya®
- Slipped Capital Femoral Epiphysis in Pediatric Patients: Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Evaluate pediatric patients receiving Sogroya® with the onset of a limp or complaints of persistent hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly
- Progression of Preexisting Scoliosis in Pediatric Patients: Monitor patients with a history of scoliosis for disease progression
- Pancreatitis: Cases of pancreatitis have been reported in patients receiving somatropin. The risk may be greater in pediatric patients compared to adults. Consider pancreatitis in patients with persistent severe abdominal pain
- Lipohypertrophy/Lipoatrophy: May occur if Sogroya® is administered at the same site over a long period of time. Rotate injection sites to reduce this risk
- Sudden Death in Pediatric Patients with Prader-Willi Syndrome: There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Sogroya® is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome
- Laboratory Tests: Serum levels of inorganic phosphorus and alkaline phosphatase have increased after Sogroya® therapy. Serum levels of parathyroid hormone may increase with somatropin treatment
Adverse Reactions
- Common adverse reactions in pediatric patients treated with Sogroya® include: cough, diarrhea, ear infection, headache, injection site reaction, nasopharyngitis, pain in extremity, pyrexia, respiratory tract infection, and vomiting
- Adult patients with GHD: Adverse reactions reported in >2% of patients are: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, blood creatine phosphokinase increase, weight increase, anemia
Drug Interactions
- Glucocorticoids: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Sogroya®
- Cytochrome P450-Metabolized Drugs: Sogroya® may alter the clearance. Monitor carefully if used with Sogroya®
- Oral Estrogen: Patients receiving oral estrogen replacement may require higher Sogroya® dosages
- Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin and/or antihyperglycemic agent may be required for patients with diabetes mellitus
Please click here for Sogroya® Prescribing Information.
Indications and Usage
Sogroya® (somapacitan-beco) injection 5 mg, 10 mg, or 15 mg is indicated for the:
- treatment of pediatric patients aged 2.5 years and older with:
- Growth failure due to inadequate secretion of endogenous growth hormone (GH)
- Short stature born Small for Gestational Age (SGA) and with no catch-up growth by 2 years of age
- Growth failure associated with Noonan Syndrome (NS)
- Idiopathic Short Stature (ISS)
- replacement of endogenous GH in adults with growth hormone deficiency (GHD)
Important Safety Information for Tresiba®
Contraindications
- Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin degludec or any of the excipients in Tresiba®
Warnings and Precautions
- Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) or who experience recurrent hypoglycemia. The long-acting effect of Tresiba® may delay recovery from hypoglycemia compared to shorter-acting insulins.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Tresiba® may vary among different patients or at different times in the same patients and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Tresiba® and other insulins, always instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove Tresiba® from the Tresiba® FlexTouch® disposable insulin prefilled pen.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Tresiba®. If hypersensitivity reactions occur, discontinue Tresiba®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Tresiba®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Tresiba®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions commonly associated with Tresiba® are hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Tresiba®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Please click here for Tresiba® Prescribing Information.
Important Safety Information for Tretten®
Tretten® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Tretten® may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.
Thromboembolic complications may occur. Monitor patients with conditions that predispose to thrombosis for signs and symptoms of thrombosis after administration of Tretten®.
Inhibitory antibodies may occur with Tretten®. Patients with inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs while receiving prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.
The most common adverse reactions reported in clinical trials (≥1%) were headache, pain in the extremities, pain at injection site, and increase in fibrin D dimer levels.
Thrombosis may occur if Tretten® is administered concomitantly with Factor VIIa.
There are no adequate and well-controlled studies using Tretten® in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with Tretten®.
Please click here for Tretten® Prescribing Information.
Important Safety Information for NovoSeven® RT
WARNING: THROMBOSIS
- Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported
- Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT
- Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis
Important Safety Information for Ozempic®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Ozempic® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Ozempic® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Ozempic® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Ozempic®
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Important Safety Information for Saxenda®
WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®.
Important Safety Information for Vagifem®
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER
Estrogen-Alone Therapy
Endometrial Cancer
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Cardiovascular Disorders and Probable Dementia
The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.
The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.
Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen Plus Progestin Therapy
Cardiovascular Disorders and Probable Dementia
The WHI estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), DVT, stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.
Breast Cancer
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Important Safety Information for Victoza®
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined
- Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Victoza® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza®
Important Safety Information for Wegovy®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Wegovy® is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Wegovy® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Wegovy®
Important Safety Information for Xultophy® 100/3.6
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide, one of the components of Xultophy® 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy® 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
- Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Xultophy® 100/3.6 and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy® 100/3.6.
Important Safety Information for GlucaGen®
Contraindications
GlucaGen® is contraindicated in patients with:
- Pheochromocytoma because of the risk of substantial increase in blood pressure
- Insulinoma because of the risk of hypoglycemia
- Known hypersensitivity to glucagon or the excipients in GlucaGen®. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension
- Glucagonoma when used as a diagnostic aid because of risk of hypoglycemia
Important Safety Information for Norditropin®
Contraindications
Norditropin® is contraindicated in patients with:
- Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin
- Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death
- Active Malignancy
- Hypersensitivity to Norditropin® or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins
- Active proliferative or severe non-proliferative diabetic retinopathy
- Pediatric patients with closed epiphyses
Important Safety Information for Sogroya®
Contraindications
Sogroya® is contraindicated in patients with:
- acute critical illness after open-heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure because of the risk of increased mortality with use of Sogroya®
- hypersensitivity to Sogroya® or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with somatropin
- pediatric patients with closed epiphyses
- active malignancy
- active proliferative or severe non-proliferative diabetic retinopathy
- pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to risk of sudden death
Important Safety Information for Tretten®
Tretten® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Tretten® may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.
Important Safety Information for NovoSeven® RT
WARNING: THROMBOSIS
- Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported
- Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT
- Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis
Warnings and Precautions
- Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance
- Patients with congenital hemophilia receiving concomitant treatment with aPCCs (activated prothrombin complex concentrates), older patients particularly with acquired hemophilia and receiving other hemostatic agents, and patients with a history of cardiac and vascular disease may have an increased risk of developing thrombotic events
- Hypersensitivity reactions, including anaphylaxis, can occur with NovoSeven® RT. Patients with a known hypersensitivity to mouse, hamster, or bovine proteins may be at a higher risk of hypersensitivity reactions. Discontinue infusion and administer appropriate treatment when hypersensitivity reactions occur
- Factor VII deficient patients should be monitored for prothrombin time (PT) and factor VII coagulant activity (FVII:C). If FVII:C fails to reach the expected level, or PT is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed
- Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis
Adverse Reactions
- The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia
Drug Interactions
- Thrombosis may occur if NovoSeven® RT is administered concomitantly with Coagulation Factor XIII
Please click here for NovoSeven® RT Prescribing Information, including Boxed Warning.
Indications and Usage
NovoSeven® RT (coagulation Factor VIIa, recombinant) is a coagulation factor indicated for:
- Treatment of bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets
- Treatment of bleeding episodes and perioperative management in adults with acquired hemophilia
Important Safety Information for Ozempic®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Ozempic® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Ozempic® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Ozempic® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Ozempic®
Contraindications
- Ozempic® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a hypersensitivity reaction to semaglutide or to any of the excipients in Ozempic®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with Ozempic®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide. Observe patients carefully for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back with or without vomiting). If pancreatitis is suspected, discontinue Ozempic® and initiate appropriate management
- Diabetic Retinopathy Complications: In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with Ozempic® (3.0%) compared with placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Never Share an Ozempic® Pen Between Patients: Ozempic® pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens
- Hypoglycemia: Patients receiving Ozempic® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Ozempic® that could lead to volume depletion, especially during dosage initiation and escalation
- Severe Gastrointestinal Adverse Reactions: Use of Ozempic® has been associated with gastrointestinal adverse reactions, sometimes severe. In Ozempic® clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Ozempic® (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%). Ozempic® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with Ozempic®. If hypersensitivity reactions occur, discontinue use of Ozempic®; treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients treated with Ozempic® 0.5 mg and 1 mg, respectively, and not reported in placebo-treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Ozempic® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Ozempic®
Adverse Reactions
- The most common adverse reactions, reported in ≥5% of patients treated with Ozempic® are nausea, vomiting, diarrhea, abdominal pain, and constipation
drug-interactions
Drug Interactions
- Updated bullet
- When initiating Ozempic®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- Ozempic® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications, so caution should be exercised
Use in Specific Populations
- There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. Discontinue Ozempic® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
Please click here for Ozempic® Prescribing Information, including Boxed Warning.
Indications and Usage
Ozempic® (semaglutide) injection 0.5 mg, 1 mg, or 2 mg is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
- to reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, or nonfatal stroke) in adults with type 2 diabetes and established CV disease
- to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease
Important Safety Information for RYBELSUS®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- RYBELSUS® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of RYBELSUS® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS®
Contraindications
- RYBELSUS® is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in RYBELSUS®. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with RYBELSUS®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including RYBELSUS®. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back), nausea or vomiting. If pancreatitis is suspected, discontinue RYBELSUS® and initiate appropriate management
- Diabetic Retinopathy Complications: In a pooled analysis of glycemic control trials with RYBELSUS®, patients reported diabetic retinopathy related adverse reactions during the trial (4.2% with RYBELSUS® and 3.8% with comparator). In a 2-year trial with semaglutide injection involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide injection (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline than among patients without a known history of diabetic retinopathy.
Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy - Hypoglycemia: Patients receiving RYBELSUS® in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to RYBELSUS® that could lead to volume depletion, especially during initiation and escalation of RYBELSUS®
- Severe Gastrointestinal Adverse Reactions: Use of RYBELSUS® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving RYBELSUS® (7 mg 0.6%, 14 mg 2%) than placebo (0.3%). RYBELSUS® is not recommended in patients with severe gastroparesis
- Hypersensitivity: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with RYBELSUS®. If hypersensitivity reactions occur, discontinue use of RYBELSUS®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials to improve glycemic control, cholelithiasis was reported in 1% of patients treated with RYBELSUS® 7 mg. In a 4-year cardiovascular outcomes trial (Trial 7), cholelithiasis was reported in 1.1% of patients treated with RYBELSUS® 14 mg and in 0.9% of placebo-treated patients. In Trial 7, cholecystitis was reported in 1.1% treated with RYBELSUS® 14 mg and in 0.7% of placebo-treated patients. If cholelithiasis or cholecystitis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: RYBELSUS® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking RYBELSUS®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation
Drug Interactions
- RYBELSUS® stimulates insulin release in the presence of elevated blood glucose concentrations. When initiating RYBELSUS®, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- RYBELSUS® delays gastric emptying and has the potential to impact the absorption of other oral medications. Closely follow RYBELSUS® administration instructions when coadministering with other oral medications and consider increased monitoring for medications with a narrow therapeutic index, such as levothyroxine
Use in Specific Populations
- Pregnancy: Available data with RYBELSUS® are not sufficient to determine a drug associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Discontinue RYBELSUS® in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide
- Lactation: A clinical lactation study reported semaglutide concentrations below the lower limit of quantification in human breast milk. However, salcaprozate sodium (SNAC) and/or its metabolites are present in human milk. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC, an absorption enhancer for RYBELSUS®, and because there are alternative formulations of semaglutide that do not contain SNAC that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with RYBELSUS®
Please click here for RYBELSUS® Prescribing Information, including Boxed Warning.
Indication and Usage
RYBELSUS® (semaglutide) tablets 7 mg or 14 mg is indicated:
- as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
- to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events
Important Safety Information for Saxenda®
WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®.
Contraindications
Saxenda® is contraindicated in:
- Patients with a personal or family history of MTC or patients with MEN 2
- Patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in Saxenda®. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Saxenda®
Warnings and Precautions
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide. Observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent or severe abdominal pain (sometimes radiating to the back), nausea or vomiting. If pancreatitis is suspected, discontinue Saxenda® and initiate appropriate management
- Acute Gallbladder Disease: Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in patients treated with Saxenda® than with placebo even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Hypoglycemia: Adult patients with type 2 diabetes on an insulin secretagogue (eg, a sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia with use of Saxenda®. The risk may be lowered by a reduction in the dose of insulin secretagogues or insulin. In pediatric patients without type 2 diabetes, hypoglycemia occurred. Inform all patients of the risk of hypoglycemia and educate them on the signs and symptoms
- Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed in patients treated with Saxenda®. Monitor heart rate at regular intervals and inform patients to report palpitations or feelings of a racing heartbeat while at rest during treatment with Saxenda®. Discontinue Saxenda® in patients who experience a sustained increase in resting heart rate
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury which may sometimes require hemodialysis, in patients treated with liraglutide. The majority of the reported events occurred in patients who had experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Saxenda® that could lead to volume depletion, especially during initation and escalation of Saxenda®
- Severe Gastrointestinal Adverse Reactions: Use of Saxenda® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Saxenda® (4.8%) than placebo (1.4%). Saxenda® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported in patients treated with Saxenda®. If a hypersensitivity reaction occurs, patients should stop taking Saxenda® and promptly seek medical advice
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Saxenda® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Saxenda®
Adverse Reactions
- The most common adverse reactions, reported in ≥5% are nausea, diarrhea, constipation, vomiting, injection site reactions, headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, upper abdominal pain, pyrexia, and gastroenteritis
Drug Interactions
- Saxenda® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. Monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®
Use in Specific Populations
- Saxenda® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- There are no data on the presence of liraglutide in human breast milk; liraglutide was present in the milk of lactating rats
- Saxenda® has not been studied in patients less than 12 years of age
Please click here for Saxenda® Prescribing Information, including Boxed Warning.
Indications and Usage
Saxenda® (liraglutide) injection 3 mg is indicated in combination with reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in:
- Adults and pediatric patients aged 12 years and older with body weight greater than 60kg and obesity
- Adults with overweight in the presence of at least one weight related comorbid condition
Limitations of Use
- Saxenda® contains liraglutide and should not be coadministered with other liraglutide-containing products or with any other GLP-1 receptor agonist
- The safety and effectiveness of Saxenda® in pediatric patients with type 2 diabetes have not been established
Important Safety Information for Vagifem®
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE DEMENTIA, and BREAST CANCER
Estrogen-Alone Therapy
Endometrial Cancer
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including directed or random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Cardiovascular Disorders and Probable Dementia
The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo.
The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.
Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Estrogen Plus Progestin Therapy
Cardiovascular Disorders and Probable Dementia
The WHI estrogen plus progestin substudy reported increased risks of pulmonary embolism (PE), DVT, stroke, and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.
The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.
Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.
Breast Cancer
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.
Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
Contraindications
- Undiagnosed abnormal genital bleeding
- Breast cancer or a history of breast cancer
- Estrogen-dependent neoplasia
- Active DVT, PE, or history of these conditions
- Active arterial thromboembolic disease (for example, stroke or MI), or a history of these conditions
- Known anaphylactic reaction, angioedema, or hypersensitivity to Vagifem®
- Hepatic impairment or disease
- Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
Warnings and Precautions
- Risks from systemic absorption: Vagifem® is intended only for vaginal administration. Systemic absorption occurs with the use of Vagifem®. The warnings, precautions, and adverse reactions associated with the use of systemic estrogen-alone therapy should be taken into account.
- Cardiovascular Disorders: Immediately discontinue estrogen with or without progestogen therapy if PE, DVT, stroke, or MI occur or are suspected.
- Malignant Neoplasms: Extension of the WHI trials also demonstrated increased breast cancer risk associated with systemic estrogen plus progestin therapy. One large meta-analysis of prospective cohort studies reported increased risks that were dependent upon duration of use of systemic estrogen plus progestin therapy and systemic estrogen-alone therapy. These risks could last up to >10 years after discontinuation of these systemic therapies depending on the duration of use. There was no increase in risk of developing breast cancer in women taking vaginal estrogens. The CE plus MPA substudy of WHI reported a statistically non-significant increased risk of ovarian cancer with the use of estrogen plus progestin. A meta-analysis of 17 prospective and 35 retrospective studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer.
- Gallbladder disease: A 2-4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
- Discontinue Vagifem® if severe hypercalcemia, visual abnormalities (sudden loss of vision, sudden onset of proptosis, diplopia, or migraine), severe hypertriglyceridemia, cholestatic jaundice or medically concerning fluid retention occurs.
- Exacerbation of Hypothyroidism: Monitor thyroid function in women on thyroid hormone replacement therapy who are also receiving estrogens because estrogen leads to increased thyroid-binding globulin (TBG) levels.
- Local abrasion: A few cases of local abrasion induced by the Vagifem® applicator have been reported.
Adverse Reactions
- The most common adverse reactions (incidence ≥5 percent) with Vagifem® are back pain, vulvovaginal pruritus, vulvovaginal mycotic infection, and diarrhea.
Drug Interactions
- Inducers and inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.
Please click here for Vagifem® Prescribing Information, including Boxed Warning.
Important Safety Information for Victoza®
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Victoza® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined
- Victoza® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Victoza® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Victoza®
Contraindications
- Victoza® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in Victoza®. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with Victoza®
Warnings and Precautions
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated
- Acute Pancreatitis: Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists, including Victoza®. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain, (sometimes radiating to the back), nausea, or vomiting. If pancreatitis is suspected, discontinue Victoza® and initiate appropriate management
- Never Share a Victoza® Pen Between Patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens
- Hypoglycemia: Adult patients receiving Victoza® in combination with an insulin secretagogue (eg, sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. In pediatric patients 10 years of age and older, the risk of hypoglycemia was higher with Victoza® regardless of insulin and/or metformin use
- Acute Kidney Injury Due to Volume Depletion : There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with Victoza®. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Victoza® that could lead to volume depletion, especially during dosage initiation and escalation of Victoza®
- Severe Gastrointestinal Adverse Reactions: Use of GLP-1 receptor agonists, including Victoza®, has been associated with gastrointestinal adverse reactions, sometimes severe. In Victoza® clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Victoza® (1.2 mg 4.4 %, 1.8 mg 4.2 %) than placebo (1.1 %). Victoza® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with Victoza®. If a hypersensitivity reaction occurs, discontinue Victoza®; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity reaction to Victoza®. Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to these reactions with Victoza®
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In the LEADER trial, 3.1% of Victoza®-treated patients versus 1.9% of placebo-treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Victoza® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Victoza®
Adverse Reactions
- The most common adverse reactions (incidence ≥5%) in clinical trials are nausea, diarrhea, vomiting, decreased appetite, dyspepsia, and constipation
- Immunogenicity-related events, including urticaria, were more common among Victoza®-treated patients (0.8%) than among comparator-treated patients (0.4%) in clinical trials
Drug Interactions
- Victoza® delays gastric emptying and may impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with Victoza®
- When initiating Victoza®, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
Use in Specific Populations
- Victoza® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
- The safety and effectiveness of Victoza® have not been established in pediatric patients less than 10 years of age
Please click here for Victoza® Prescribing Information, including Boxed Warning.
Indications and Limitations of Use
Victoza® (liraglutide) injection 1.2 mg or 1.8 mg is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes and established cardiovascular disease.
- Victoza® contains liraglutide and should not be coadministered with other liraglutide-containing products
Important Safety Information for Wegovy®
WARNING: RISK OF THYROID C-CELL TUMORS
- In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined
- Wegovy® is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Wegovy® and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Wegovy®
Contraindications
- Wegovy® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, and in patients with a prior serious hypersensitivity reaction to semaglutide or to any of the excipients in Wegovy®. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported with Wegovy®
Warnings and Precautions
- Risk of Thyroid C-Cell Tumors: Patients should be further evaluated if serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including Wegovy®. Observe patients carefully for signs and symptoms of acute pancreatitis, which may include persistent severe abdominal pain (sometimes radiating to the back), nausea, or vomiting. If acute pancreatitis is suspected, discontinue Wegovy® and initiate appropriate management
- Acute Gallbladder Disease: Treatment with Wegovy® is associated with an increased occurrence of cholelithiasis and cholecystitis. The incidence of cholelithiasis and cholecystitis was higher in Wegovy® pediatric patients aged 12 years and older than in Wegovy® adults. In clinical trials in adult patients for weight reduction, cholelithiasis was reported by 1.6% of Wegovy® patients and 0.7% of placebo patients. Cholecystitis was reported by 0.6% of Wegovy® patients and 0.2% of placebo patients. In a clinical trial in pediatric patients aged 12 years and older for weight reduction, cholelithiasis was reported by 3.8% of Wegovy® patients and 0% placebo patients. Cholecystitis was reported by 0.8% of Wegovy® pediatric patients and 0% placebo patients. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Wegovy® patients than in placebo patients, even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated
- Hypoglycemia: Wegovy® lowers blood glucose and can cause hypoglycemia. In a trial of adult patients with type 2 diabetes for weight reduction, hypoglycemia was reported in 6.2% of Wegovy® patients versus 2.5% of placebo patients. Patients with diabetes taking Wegovy® with an insulin or insulin secretagogue (e.g. sulfonylurea) may have an increased risk of hypoglycemia, including severe hypoglycemia. The use of Wegovy® in patients with type 1 diabetes or in combination with insulin has not been evaluated. Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms. Monitor blood glucose in patients with diabetes
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea. Monitor renal function in patients reporting adverse reactions to Wegovy® that could lead to volume depletion, especially during initiation and escalation of Wegovy®
- Severe Gastrointestinal Adverse Reactions: Use of Wegovy® has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials in adults for weight reduction, severe gastrointestinal adverse reactions were reported more frequently among patients receiving Wegovy® (4.1%) than placebo (0.9%). Wegovy® is not recommended in patients with severe gastroparesis
- Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with Wegovy®. If hypersensitivity reactions occur, discontinue use of Wegovy®, treat promptly per standard of care, and monitor until signs and symptoms resolve. Use caution in a patient with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist
- Diabetic Retinopathy Complications in Patients with Type 2 Diabetes: In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m2 for weight reduction, diabetic retinopathy was reported by 4.0% of Wegovy® patients and 2.7% of placebo patients. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy
- Heart Rate Increase: Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed in Wegovy® adult patients compared to placebo in weight reduction clinical trials. More Wegovy® adult patients compared with placebo had maximum changes from baseline of 10 to 19 bpm (41% versus 34%) and 20 bpm or more (26% versus 16%). In a clinical trial for weight reduction in pediatric patients aged 12 years and older with normal baseline heart rate, more patients treated with Wegovy® compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%). Monitor heart rate at regular intervals and instruct patients to report palpitations or feelings of a racing heartbeat while at rest. If patients experience a sustained increase in resting heart rate, discontinue Wegovy®
- Suicidal Behavior and Ideation: Suicidal behavior and ideation have been reported in clinical trials with other weight management products. Monitor patients for depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Wegovy® in patients who experience suicidal thoughts or behaviors and avoid in patients with a history of suicidal attempts or active suicidal ideation
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Wegovy® delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Wegovy®
Adverse Reactions
- Most common adverse reactions (incidence ≥5%) are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distention, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis
Drug Interactions
- The addition of Wegovy® in patients treated with insulin has not been evaluated. When initiating Wegovy®, consider reducing the dose of concomitantly administered insulin secretagogues (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia
- Wegovy® causes a delay of gastric emptying and has the potential to impact the absorption of concomitantly administered oral medications. Monitor the effects of oral medications concomitantly administered with Wegovy®
Use in Specific Populations
- Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Wegovy®. Discontinue Wegovy® in patients at least 2 months before a planned pregnancy
- Pediatric: Adverse reactions with Wegovy® in pediatric patients aged 12 years and older with obesity were similar to those reported in adults in weight reduction trials. Pediatric patients ≥12 years of age treated with Wegovy® had greater incidences of cholelithiasis, cholecystitis, hypotension, rash, and urticaria compared to adults treated with Wegovy®. There are insufficient data in pediatric patients with type 2 diabetes treated with Wegovy® for obesity to determine if there is an increased risk of hypoglycemia with Wegovy® treatment similar to that reported in adults
- Geriatric: In the cardiovascular outcomes trial, patients aged 75 years and older reported more hip and pelvis fractures on Wegovy® than placebo. Patients aged 75 years and older (Wegovy® and placebo) reported more serious adverse reactions overall compared to younger adult patients
Please click here for Wegovy® Prescribing Information, including Boxed Warning.
Indications and Usage
Wegovy® (semaglutide) injection 2.4 mg is indicated in combination with a reduced calorie diet and increased physical activity:
- for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) in adults.
The indication for MASH is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon the verification and description of clinical benefit in a confirmatory trial. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight
- to reduce excess body weight and maintain weight reduction long term in adults and pediatric patients aged 12 years and older with obesity and adults with overweight in the presence of at least one weight-related comorbidity
Limitations of Use:
Wegovy® contains semaglutide. Coadministration with other semaglutide-containing products or with any GLP-1 receptor agonist is not recommended
Important Safety Information for Xultophy® 100/3.6
WARNING: RISK OF THYROID C-CELL TUMORS
- Liraglutide, one of the components of Xultophy® 100/3.6, causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Xultophy® 100/3.6 causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
- Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of Xultophy® 100/3.6 and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Xultophy® 100/3.6.
CONTRAINDICATIONS
- Xultophy® 100/3.6 is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), during episodes of hypoglycemia, and in patients with hypersensitivity to Xultophy® 100/3.6, either of the active substances, or any of its excipients. Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with liraglutide, one of the components of Xultophy® 100/3.6.
WARNINGS AND PRECAUTIONS
- Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated or thyroid nodules are noted on physical examination or neck imaging, the patient should be further evaluated.
- Acute Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including liraglutide, one of the components of Xultophy® 100/3.6. Observe patients carefully for signs and symptoms of acute pancreatitis which may include persistent or severe abdominal pain (sometimes radiating to the back) nausea or vomiting. If pancreatitis is suspected, discontinue Xultophy® 100/3.6 and initiate appropriate management.
- Never Share a Xultophy® 100/3.6 Pen Between Patients, even if the needle is changed. Sharing of the pen poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Overdose Due to Medication Errors: Instruct patients to check the label before each injection since accidental mix-ups with insulin containing products can occur. Do not administer more than 50 units of Xultophy® 100/3.6 daily. Do not exceed the 1.8 mg maximum recommended dose of liraglutide or use with other GLP-1 RAs.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin-containing products, including Xultophy® 100/3.6. Severe hypoglycemia can cause seizures, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time which may place the patient and others at risk in situations where these abilities are important. Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, diabetic neuropathy, and in patients using drugs that block the sympathetic nervous system, or who experience recurrent hypoglycemia. The long-acting effect of insulin degludec may delay recovery from hypoglycemia compared to shorter acting insulins. Increase monitoring with changes to: dose, co-administered glucose lowering medications, concomitant drugs, meal pattern, physical activity; and in patients with hypoglycemia unawareness or renal or hepatic impairment.
- Acute Kidney Injury Due to Volume Depletion: There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with liraglutide, one of the components of Xultophy® 100/3.6. The majority of reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting or diarrhea. Monitor renal function in patients reporting adverse reactions to Xultophy® 100/3.6 that could lead to volume depletion, especially during initiation and escalation of Xultophy® 100/3.6.
- Severe Gastrointestinal Adverse Reactions: Use of GLP-1 receptor agonists, including liraglutide, one of the components of Xultophy® 100/3.6, has been associated with gastrointestinal adverse reactions, sometimes severe. In a Xultophy® 100/3.6 clinical trial severe gastrointestinal adverse reactions were reported among patients receiving Xultophy® 100/3.6 (0.8 %) and patients receiving the active comparators liraglutide (2.9%) and insulin degludec (0.2%). Xultophy® 100/3.6 is not recommended in patients with severe gastroparesis.
- Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, angioedema, bronchospasm, hypotension, and shock can occur with insulins, including Xultophy® 100/3.6. There have been postmarketing reports of serious hypersensitivity reactions (e.g. anaphylactic reactions and angioedema) in patients treated with liraglutide, one of the components of Xultophy® 100/3.6. If a hypersensitivity reaction occurs, discontinue and treat promptly per standard of care, and monitor until signs and symptoms resolve. Anaphylaxis and angioedema have been reported with other GLP-1 RAs. Use caution in a patient with a history of anaphylaxis or angioedema with other GLP-1 RAs because it is unknown whether such patients will be predisposed to these reactions with Xultophy® 100/3.6.
- Acute Gallbladder Disease: Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In a cardiovascular outcomes trial (LEADER trial) 3.1% of patients treated with liraglutide, one of the components of Xultophy® 100/3.6, versus 1.9% of placebo treated patients reported an acute event of gallbladder disease, such as cholelithiasis or cholecystitis. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
- Hypokalemia: All insulin containing products, including Xultophy® 100/3.6 can lead to life-threatening hypokalemia, which may then cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Congestive Heart Failure: Patients using insulin containing products, including Xultophy® 100/3.6, with thiazolidinediones (TZDs) should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.
- Pulmonary Aspiration During General Anesthesia or Deep Sedation: Xultophy® 100/3.6 delays gastric emptying. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking Xultophy® 100/3.6.
ADVERSE REACTIONS
- The most common adverse reactions, reported in ≥5% of patients treated with Xultophy® 100/3.6 are nasopharyngitis, headache, nausea, diarrhea, increased lipase and upper respiratory tract infection.
DRUG INTERACTIONS
- Certain drugs may affect glucose metabolism, requiring dose adjustment and close monitoring of blood glucose. The signs and symptoms of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine).
- Liraglutide-containing products, including Xultophy® 100/3.6, cause a delay of gastric emptying, and thereby have the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with liraglutide-containing products.
USE IN SPECIFIC POPULATIONS
- Xultophy® 100/3.6 should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Please click here for Xultophy® 100/3.6 Prescribing Information, including Boxed Warning.
Indications and Limitations of Use
Xultophy® 100/3.6 (insulin degludec and liraglutide) injection 100 units/mL and 3.6 mg/mL is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Xultophy® 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist (GLP-1 RA).
- Xultophy® 100/3.6 is not recommended for the treatment of diabetic ketoacidosis.
- Xultophy® 100/3.6 has not been studied in combination with prandial insulin.
Important Safety Information for Alhemo®
Contraindications
- Alhemo® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo® or its ingredients
Warnings and Precautions
- Thromboembolic Events (TEs): Venous and arterial TEs were reported in 1.9% of patients (6/320) who also had multiple risk factors, including the use of high doses or prolonged treatment with factor product or bypassing agent (2 of 6 patients). Risk factors for TEs may also include conditions in which tissue factor is overexpressed (eg, atherosclerotic disease, crush injury, cancer, disseminated intravascular coagulation, thrombotic microangiopathy, or septicemia). Inform patients about and monitor them for signs and symptoms of TEs. In case of suspicion of TEs, discontinue Alhemo® and initiate further investigations and management strategies
- Hypersensitivity Reactions: Alhemo® is contraindicated in patients with a history of known serious hypersensitivity to Alhemo® or its ingredients. Hypersensitivity reactions, including erythema, rash, pruritus, and abdominal pain, have occurred in patients treated with Alhemo®. One patient (<1%) experienced anaphylaxis, which resolved after treatment with antihistamines and corticosteroids. Instruct patients of the signs of acute hypersensitivity reactions and to contact their healthcare provider for mild reactions and to seek urgent medical attention for moderate to severe reactions. Discontinue Alhemo® if severe hypersensitivity symptoms occur and initiate medical management
- Increased Laboratory Values of Fibrin D-dimer and Prothrombin Fragment 1.2: Increased levels of fibrin D-dimer and prothrombin fragment 1.2 were seen in 29 (9.1%) and 26 (8.1%) patients, respectively, which is positively correlated with the plasma concentration of concizumab-mtci, indicating a hemostatic effect. For patients taking Alhemo®, these coagulation biomarkers may not be reliable predictive markers for clinical decision-making with suspicion of thrombosis, such as deep vein thrombosis and pulmonary embolism
Adverse Reactions
- The most frequently reported adverse reactions (≥5%) were injection site reactions, headache, and urticaria
- Serious adverse reactions were reported in 6.1% of patients with inhibitors who received Alhemo®. Permanent discontinuation of Alhemo® occurred in 1 patient due to a renal infarct and dosage interruptions of Alhemo® occurred in 1 patient (3%) and was a hypersensitivity reaction
Drug Interactions
- Breakthrough Bleeding Treatment: Take appropriate precautions when treating breakthrough bleeding events in patients receiving Alhemo® prophylaxis and FVIII or FIX or a bypassing agent (eg, rFVIIa or aPCC). For mild and moderate bleeds, the lowest approved dose in the approved product labeling is recommended. For aPCC, a maximum dose of 100 units/kg within 24 hours is recommended. For severe bleeds, follow the dosing instructions in the approved labeling based on clinical judgment
Please click here for Alhemo® Prescribing Information.
Indications and Usage
Alhemo® (concizumab-mtci) injection 60 mg, 150 mg, or 300 mg is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or B with or without Factor VIII or IX inhibitors.
Important Safety Information for Esperoct®
Contraindications
- Do not use in patients who have known hypersensitivity to Esperoct® or its components, including hamster proteins
Warnings and Precautions
- Hypersensitivity reactions, including anaphylaxis, may occur. Should hypersensitivity reactions occur, discontinue Esperoct® and administer appropriate treatment
- Development of neutralizing antibodies (inhibitors) has occurred. Perform an assay that measures Factor VIII inhibitor concentration if bleeding is not controlled with the recommended dose of Esperoct® or if the expected plasma Factor VIII activity levels are not attained
- Temporary decrease in Factor VIII incremental recovery (IR) has been observed after Esperoct® infusion, within the first 5 exposure days, in previously untreated patients (PUPs) <6 years of age. During the decreased IR period, these subjects may have an increased bleeding tendency. If bleeding is not controlled with the recommended dose of Esperoct® and/or the expected Factor VIII activity levels are not attained and Factor VIII inhibitors are not detected, consider adjusting the dose, dosing frequency, or discontinuing Esperoct®
Adverse Reactions
- The most frequently reported adverse reactions in clinical trials (≥1%) were rash, redness, itching (pruritus), and injection site reactions. Additional frequently reported adverse reactions (≥1%) in PUPs included Factor VIII inhibition and hypersensitivity.
Please click here for Esperoct® Prescribing Information.
Indications and Usage
Esperoct® [antihemophilic factor (recombinant), glycopegylated-exei] is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes
- Esperoct® is not indicated for the treatment of von Willebrand disease
Important Safety Information for Fiasp®
Contraindications
- Fiasp® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to Fiasp® or one of its excipients.
Warnings and Precautions
- Never share a Fiasp® FlexTouch® Pen, PenFill® cartridge or PenFill® cartridge device between patients, even if the needle is changed. Patients using Fiasp® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia is the most common adverse reaction of insulin, including Fiasp®, and may be life-threatening. Increase glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness.
- To avoid medication errors and accidental mix-ups between Fiasp® and other insulin products, instruct patients to always check the insulin label before injection.
- As with all insulins, Fiasp® use can lead to life-threatening hypokalemia, which then may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including Fiasp®.
- Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Fiasp®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
- Pump or infusion set malfunctions can lead to a rapid onset of hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim therapy with subcutaneous injection of Fiasp® may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.
Drug Interactions
- Drugs That May Increase the Risk of Hypoglycemia: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics. Dose reductions and increased frequency of glucose monitoring may be required.
- Drugs That May Decrease the Blood Glucose Lowering Effect of Fiasp®: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Dose increases and increased frequency of glucose monitoring may be required.
- Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Fiasp®: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Dose adjustment and increased frequency of glucose monitoring may be required.
- Drugs That May Blunt Signs and Symptoms of Hypoglycemia: Beta-blockers, clonidine, guanethidine, and reserpine. Increased frequency of glucose monitoring may be required
Adverse Reactions
- Adverse reactions observed with Fiasp® include hypoglycemia, allergic reactions, hypersensitivity, injection site reactions, lipodystrophy, and weight gain.
Use in Specific Populations
- Pediatric patients with type 1 diabetes treated with mealtime and postmeal Fiasp® reported a higher rate of blood glucose confirmed hypoglycemic episodes compared to patients treated with NovoLog® (insulin aspart) injection; the imbalance was greater during the nocturnal period. Monitor blood glucose levels closely in pediatric patients.
- Like all insulins, Fiasp® requirements may be reduced in patients with renal impairment or hepatic impairment. These patients may require more frequent blood glucose monitoring and dose adjustments.
Please click here for Fiasp® Prescribing Information.
Important Safety Information for GlucaGen®
Contraindications
GlucaGen® is contraindicated in patients with:
- Pheochromocytoma because of the risk of substantial increase in blood pressure
- Insulinoma because of the risk of hypoglycemia
- Known hypersensitivity to glucagon or the excipients in GlucaGen®. Allergic reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension
- Glucagonoma when used as a diagnostic aid because of risk of hypoglycemia
Warnings and Precautions
- Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: GlucaGen® is contraindicated in patients with pheochromocytoma because GlucaGen® may stimulate the release of catecholamines from the tumor.
- Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, GlucaGen® administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GlucaGen® is contraindicated in patients with insulinoma. If a patient develops symptoms of hypoglycemia after a dose of GlucaGen®, give glucose orally or intravenously.
- Hypersensitivity and Allergic Reactions: Allergic reactions have been reported with glucagon, these include generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. GlucaGen® is contraindicated in patients with a prior hypersensitivity reaction.
- Lack of Efficacy in Patients with Decreased Hepatic Glycogen: GlucaGen® is effective in treating hypoglycemia only if sufficient hepatic glycogen is present. Patients in states of starvation, with adrenal insufficiency or chronic hypoglycemia may not have adequate levels of hepatic glycogen for GlucaGen® administration to be effective. Patients with these conditions should be treated with glucose.
- Necrolytic Migratory Erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, has been reported post-marketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.
- Hyperglycemia in Patients with Diabetes Mellitus when Used as a Diagnostic Aid: Treatment with GlucaGen® in patients with diabetes mellitus may cause hyperglycemia. Monitor diabetic patients for changes in blood glucose levels during treatment and treat if indicated.
- Blood Pressure and Heart Rate Increase in Patients with Cardiac Disease when used as a Diagnostic Aid: GlucaGen® may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life-threatening in patients with cardiac disease. Cardiac monitoring is recommended in patients with cardiac disease during use of GlucaGen® as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy.
- Hypoglycemia in Patients with Glucagonoma: Glucagon administered to patients with glucagonoma may cause secondary hypoglycemia. Test patients suspected of having glucagonoma for blood levels of glucagon prior to use as a diagnostic aid as GlucaGen® is contraindicated in this setting.
Adverse Reactions
- Glucagon adverse reactions identified during post approval use are: injection site reactions, nausea, vomiting, headache, dizziness, asthenia, pallor, diarrhea, somnolence, and decreased blood pressure.
Drug Interactions
- Beta-blockers patients taking beta-blockers may have a transient increase in pulse and blood pressure.
- Indomethacin: In patients taking indomethacin, GlucaGen® may lose its ability to raise blood glucose or may produce hypoglycemia.
- Anticholinergic Drugs: Concomitant use of anticholinergic drugs with GlucaGen® for use as a diagnostic aid is not recommended.
- Warfarin: GlucaGen® may increase the anticoagulant effect of warfarin.
- Insulin: Monitor blood glucose when GlucaGen® is used as a diagnostic aid in patients receiving insulin.
Please click here for GlucaGen® Prescribing Information.
Indications and Usage
GlucaGen® (glucagon) for injection 1mg/mL is an antihypoglycemic agent and a gastrointestinal motility inhibitor indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes and as a diagnostic aid for use during radiologic examinations to temporarily inhibit movement of the gastrointestinal tract in adult patients.
Important Safety Information for Levemir®
Contraindications
- Levemir® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to insulin detemir or any of the excipients in Levemir®. Reactions have included anaphylaxis.
Warnings and Precautions
- Never Share a Levemir® FlexPen® prefilled pen, Needle, or Syringe Between Patients: Levemir® FlexPen® prefilled pens must never be shared between patients, even if the needle is changed. Patients using Levemir® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Levemir®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers), or who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Levemir® may vary among different patients or at different times in the same patient and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. When a GLP-1 receptor agonist is used in combination with Levemir®, the Levemir® dose may need to be lowered or more conservatively titrated to minimize the risk of hypoglycemia. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Levemir® and other insulins, instruct patients to always check the insulin label before each injection.
- Hypersensitivity and Allergic Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin, including Levemir®. If hypersensitivity reactions occur, discontinue Levemir®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Levemir®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including Levemir®, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.
Adverse Reactions
- Adverse reactions associated with Levemir® include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, rash, and pruritus.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Levemir®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Use in Specific Populations
- Pregnancy: Available data from published studies and postmarketing case reports with Levemir® use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
- Clinical Considerations - Disease-Associated Maternal and/or Embryo/Fetal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
- Clinical Considerations - Disease-Associated Maternal and/or Embryo/Fetal Risk: Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
Please click here for Levemir® Prescribing Information.
Important Safety Information for Norditropin®
Contraindications
Norditropin® is contraindicated in patients with:
- Acute critical illness after open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure due to the risk of increased mortality with use of pharmacologic doses of somatropin
- Pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to the risk of sudden death
- Active Malignancy
- Hypersensitivity to Norditropin® or any of its excipients. Systemic hypersensitivity reactions have been reported with postmarketing use of somatropins
- Active proliferative or severe non-proliferative diabetic retinopathy
- Pediatric patients with closed epiphyses
Warnings and Precautions
- Increased mortality in patients with acute critical illness due to complications following open heart or abdominal surgery or multiple accidental trauma, or those with respiratory failure has been reported.
- Sudden death in pediatric patients with Prader-Willi Syndrome has been reported after initiating treatment with somatropin with one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Evaluate patients for signs of upper airway obstruction and sleep apnea before initiation of treatment.
- Increased risk of neoplasms: Monitor patients with preexisting tumors for progression or recurrence. In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm, in particular meningiomas, has been reported. Pediatric patients with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients carefully for increased growth, or potential malignant changes of preexisting nevi.
- Glucose intolerance and diabetes mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New-onset type 2 diabetes mellitus has been reported. Monitor glucose levels in all patients. Doses of concurrent antidiabetic drugs may require adjustment.
- Intracranial hypertension has been reported in a small number of patients, usually within the first 8 weeks of somatropin treatment. Funduscopic examination should be performed before initiating treatment and periodically thereafter.
- Severe hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropins.
- Fluid retention in adults (clinically manifesting as edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) may frequently occur and is usually transient and dose dependent.
- Hypoadrenalism: Patients who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Norditropin® treatment.
- Hypothyroidism if undiagnosed/untreated, may prevent an optimal response to Norditropin®, in particular, the growth response in pediatric patients. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or adjusted when indicated.
- Slipped capital femoral epiphysis in pediatric patients may occur more frequently in patients with endocrine disorders or in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin, including Norditropin®. Evaluate pediatric patients receiving Norditropin® with the onset of a limp or complaints of hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly.
- Progression of preexisting scoliosis in pediatric patients can occur in patients who experience rapid growth. Patients with a history of scoliosis should be monitored for progression.
- Pancreatitis: Cases of pancreatitis have been reported. Pancreatitis should be considered in any patient who develops persistent severe abdominal pain.
- Lipoatrophy: Tissue atrophy may result when somatropin is administered subcutaneously at the same site over a long period of time. Rotate injection sites when administering Norditropin® to reduce this risk.
Adverse Reactions
- Common adverse reactions in adults and pediatric patients include: upper respiratory infection, fever, pharyngitis, headache, otitis media, edema, arthralgia, paresthesia, myalgia, peripheral edema, flu syndrome, and impaired glucose tolerance
Drug Interactions
- Glucocorticoids: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Norditropin®
- Pharmacologic Glucocorticoid Therapy and Supraphysiologic Glucocorticoid Treatment: Adjust glucocorticoid replacement dosing in pediatric patients receiving glucocorticoid treatment to avoid both hypoadrenalism and an inhibitory effect on growth
- Cytochrome P450-Metabolized Drugs: Norditropin® may alter the clearance. Monitor carefully if used with Norditropin®
- Oral Estrogen: Larger doses of Norditropin® may be required
- Insulin and/or Other Hypoglycemic Agents: Dose adjustment of insulin or hypoglycemic agent may be required
Use in Specific Populations
- Pregnancy and Nursing Mothers: There are limited data with somatropin use in pregnant women and nursing mothers to inform a drug-associated risk for adverse developmental outcomes
- Geriatric Use: The safety and effectiveness in patients aged 65 and over has not been evaluated in clinical studies
Please click here for Norditropin® Prescribing Information.
Indications and Usage
Norditropin® (somatropin) injection 5 mg, 10 mg, or 15 mg is indicated for the treatment of pediatric patients with:
- growth failure due to inadequate secretion of endogenous growth hormone (GH)
- short stature associated with Noonan syndrome
- short stature associated with Turner syndrome
- short stature born small for gestational age (SGA) with no catch-up growth by age 2 to 4 years of age
- Idiopathic Short Stature (ISS), height standard deviation score (SDS) <-2.25, and associated with growth rates unlikely to permit attainment of adult height in the normal range
- growth failure due to Prader-Willi syndrome (PWS)
Norditropin® is also indicated for the replacement of endogenous GH in adults with growth hormone deficiency (GHD)
Important Safety Information for Novoeight®
Contraindications
- Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to Novoeight® or its components, including hamster proteins
Warnings and Precautions
- Anaphylaxis and severe hypersensitivity reactions are possible. Patients may develop hypersensitivity to hamster proteins, which are present in trace amounts in the product. Should symptoms occur, discontinue Novoeight® and administer appropriate treatment
- Development of activity-neutralizing antibodies (inhibitors) may occur. Previously untreated patients (PUPs) are at greatest risk for inhibitor development with all factor VIII products. Inhibitors have been reported following administration of Novoeight® in PUPs. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform testing for factor VIII inhibitors
Adverse Reactions
- The most frequently reported adverse reactions (≥1%) were inhibitors in Previously Untreated Patients (PUPs), injection site reactions, and pyrexia.
Please click here for Novoeight® Prescribing Information.
Indications and Usage
Novoeight® (antihemophilic factor, recombinant) is indicated for use in adults and children with hemophilia A for on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis to reduce the frequency of bleeding episodes.
- Novoeight® is not indicated for the treatment of von Willebrand disease
Important Safety Information for NovoLog®
Contraindications
- NovoLog® is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® or one of its excipients.
Warnings and Precautions
- Never Share a NovoLog® FlexPen, NovoLog® FlexTouch®, PenFill® Cartridge, or PenFill® Cartridge Device Between Patients, even if the needle is changed. Patients using NovoLog® vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse effect of all insulins, including NovoLog®. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers), or in patients who experience recurrent hypoglycemia.
- Risk Factors for Hypoglycemia: The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of NovoLog® may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to co-administered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia.
- Hypoglycemia Due to Medication Errors: To avoid medication errors and accidental mix-ups between NovoLog® and other insulin products, instruct patients to always check the insulin label before injection.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulin products, including NovoLog®.
- Hypokalemia: All insulins, including NovoLog®, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
- Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction: Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Patients using insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.
NovoLog® continuous subcutaneous infusion route (insulin pump): Do not mix NovoLog® with any other insulin or diluent.
Adverse Reactions
- Adverse reactions observed with NovoLog® include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus.
Drug Interactions
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine.
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.
Please click here for NovoLog® Prescribing Information.
Important Safety Information for NovoLog® Mix 70/30
Contraindications
- NovoLog® Mix 70/30 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® Mix 70/30 or one of its excipients.
Warnings and Precautions
- Never Share a NovoLog® Mix 70/30 FlexPen®, Needle, or Syringe Between Patients, even if the needle is changed. Patients using NovoLog® Mix 70/30 vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse effect of all insulins, including NovoLog® Mix 70/30. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers), or in patients who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia: The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of NovoLog® Mix 70/30 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to co-administered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. - Hypoglycemia Due to Medication Errors: To avoid medication errors and accidental mix-ups between NovoLog® Mix 70/30 and other insulins, instruct patients to always check the insulin label before injection.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with insulins, including NovoLog® Mix 70/30. If hypersensitivity reactions occur, discontinue NovoLog® Mix 70/30; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including NovoLog® Mix 70/30, can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentration).
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including NovoLog® Mix 70/30. Patients should be observed for signs and symptoms of heart failure. If heart failure develops, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions observed with insulin therapy include hypoglycemia, allergic reactions, local injection site reactions, lipodystrophy, rash, and pruritus.
Use in Specific Populations
- The safety and effectiveness of NovoLog® Mix 70/30 have not been established in pediatric patients. Clinical studies of NovoLog® Mix 70/30 did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Drug Interactions
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics.
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine.
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine.
Please click here for NovoLog® Mix 70/30 Prescribing Information.
Indications and Usage
- NovoLog® Mix 70/30 (insulin aspart protamine and insulin aspart) injectable suspension 100 U/mL is a mixture of insulin aspart protamine and insulin aspart indicated to improve glycemic control in adult patients with diabetes mellitus.
Important Limitations of Use
- NovoLog® Mix 70/30 is not recommended for the treatment of diabetic ketoacidosis.
- The proportions of rapid-acting and long-acting insulins are fixed and do not allow for basal versus prandial dose adjustments.
Important Safety Information for Rebinyn®
Contraindications
- Rebinyn® is contraindicated in patients with a known hypersensitivity to Rebinyn® or its components, including hamster proteins.
Warnings and Precautions
- Hypersensitivity Reactions: Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with Rebinyn®. Signs may include angioedema, chest tightness, difficulty breathing, wheezing, urticaria, and itching. Discontinue Rebinyn® if allergic- or anaphylactic-type reactions occur and initiate appropriate treatment.
- Inhibitors: The formation of inhibitors (neutralizing antibodies) to Factor IX has occurred following Rebinyn®. If expected plasma factor IX activity levels are not attained, or if bleeding is not controlled as expected with the administered dose, perform an assay that measures Factor IX inhibitor concentration. Monitor all patients using clinical observations and laboratory tests for the development of inhibitors. Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.
- Thrombotic Events: The use of Factor IX-containing products has been associated with thromboembolic complications. Monitor for thrombotic and consumptive coagulopathy when administering Rebinyn® to patients with liver disease, post-operatively, to newborn infants, or to patients at risk of thrombosis or disseminated intravascular coagulation (DIC).
- Nephrotic Syndrome: Nephrotic syndrome has been reported following immune tolerance induction therapy with Factor IX products in hemophilia B patients with Factor IX inhibitors, often with a history of allergic reactions to Factor IX. The safety and efficacy of using Rebinyn® for immune tolerance induction have not been established.
Adverse Reactions
- The most common adverse reactions reported in previously treated patients in clinical trials (≥1%) were itching and injection site reactions. The most common adverse reactions (≥1%) in previously untreated patients reported in clinical trials were rash, FIX inhibitors, hypersensitivity, itching, injection site reaction, and anaphylactic reaction.
- Animals administered Rebinyn® showed accumulation of PEG in the choroid plexus, pituitary, circumventricular organs, and cranial motor neurons. The potential clinical implications of these animal findings are unknown. Consider whether the patient is vulnerable to cognitive impairment, such as infants and children who have developing brains, and patients who are cognitively impaired.
Please click here for Rebinyn® Prescribing Information.
Indications and Usage
Rebinyn®, Coagulation Factor IX (Recombinant), GlycoPEGylated, is a recombinant DNA derived coagulation Factor IX concentrate indicated for use in adults and children with hemophilia B (congenital Factor IX deficiency) for on demand treatment and control of bleeding episodes, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes.
Limitations of Use: Rebinyn® is not indicated for immune tolerance induction in patients with hemophilia B.
Important Safety Information for Rivfloza®
Adverse Reactions
Most common adverse reactions (reported in ≥20% of patients) are injection site reactions, which include erythema, pain, bruising, and rash.
Please click here for Rivfloza® Prescribing Information.
Important Safety Information for Sogroya®
Contraindications
Sogroya® is contraindicated in patients with:
- acute critical illness after open-heart surgery, abdominal surgery, multiple accidental trauma, or acute respiratory failure because of the risk of increased mortality with use of Sogroya®
- hypersensitivity to Sogroya® or any of its excipients. Systemic hypersensitivity reactions have been reported postmarketing with somatropin
- pediatric patients with closed epiphyses
- active malignancy
- active proliferative or severe non-proliferative diabetic retinopathy
- pediatric patients with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnea, or have severe respiratory impairment due to risk of sudden death
Warnings & Precautions
- Increased Mortality in Patients with Acute Critical Illness: Increased mortality has been reported after treatment with somatropin in patients with acute critical illness due to complications following open-heart surgery, abdominal surgery, multiple accidental trauma, and in patients with acute respiratory failure
- Severe Hypersensitivity: Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported postmarketing with use of somatropin. Inform patients and/or caregivers that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs
- Increased Risk of Neoplasms: There is an increased risk of malignancy progression with somatropin in patients with active malignancy. Any preexisting malignancy should be inactive, and its treatment complete prior to instituting Sogroya®. In childhood cancer survivors treated with radiation to the brain/head for their first neoplasm who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Monitor patients with a history of GHD secondary to an intracranial neoplasm for progression or recurrence of the tumor. Children with certain rare genetic causes of short stature have an increased risk of developing malignancies and should be carefully monitored for development of neoplasms. Monitor patients for increased growth or potential malignant changes of preexisting nevi. Advise patients/caregivers to report changes in the appearance of preexisting nevi
- Glucose Intolerance and Diabetes Mellitus: Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses. New onset type 2 diabetes has been reported. Monitor glucose levels in all patients, especially in those with existing diabetes mellitus or with risk factors for diabetes mellitus, such as obesity, Turner syndrome, or a family history of diabetes mellitus. The doses of antidiabetic agents may require adjustment when Sogroya® is initiated
- Intracranial Hypertension: Has been reported usually within 8 weeks of treatment initiation. Perform fundoscopic examination prior to initiation of treatment and periodically thereafter. If papilledema is identified, evaluate the etiology, and treat the underlying cause before initiating Sogroya®. If papilledema is observed, stop treatment. If intracranial hypertension is confirmed, Sogroya® can be restarted at a lower dose after intracranial hypertension signs and symptoms have resolved
- Fluid Retention: Was observed during Sogroya® therapy. Clinical manifestations of fluid retention (e.g. edema and nerve compression syndromes, including carpal tunnel syndrome/paresthesia) are usually transient and dose dependent
- Hypoadrenalism: Patients receiving somatropin therapy who have or are at risk for corticotropin deficiency may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Sogroya®. Monitor patients with known hypoadrenalism for reduced serum cortisol levels and/or need for glucocorticoid dose increases
- Hypothyroidism: Undiagnosed/untreated hypothyroidism may prevent an optimal response to Sogroya®. Monitor thyroid function periodically as hypothyroidism may occur or worsen after initiation of Sogroya®
- Slipped Capital Femoral Epiphysis in Pediatric Patients: Slipped capital femoral epiphysis may occur more frequently in patients undergoing rapid growth. Slipped capital femoral epiphysis may lead to osteonecrosis. Cases of slipped capital femoral epiphysis with or without osteonecrosis have been reported in pediatric patients with short stature receiving somatropin. Evaluate pediatric patients receiving Sogroya® with the onset of a limp or complaints of persistent hip or knee pain for slipped capital femoral epiphysis and osteonecrosis and manage accordingly
- Progression of Preexisting Scoliosis in Pediatric Patients: Monitor patients with a history of scoliosis for disease progression
- Pancreatitis: Cases of pancreatitis have been reported in patients receiving somatropin. The risk may be greater in pediatric patients compared to adults. Consider pancreatitis in patients with persistent severe abdominal pain
- Lipohypertrophy/Lipoatrophy: May occur if Sogroya® is administered at the same site over a long period of time. Rotate injection sites to reduce this risk
- Sudden Death in Pediatric Patients with Prader-Willi Syndrome: There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Sogroya® is not indicated for the treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome
- Laboratory Tests: Serum levels of inorganic phosphorus and alkaline phosphatase have increased after Sogroya® therapy. Serum levels of parathyroid hormone may increase with somatropin treatment
Adverse Reactions
- Common adverse reactions in pediatric patients treated with Sogroya® include: cough, diarrhea, ear infection, headache, injection site reaction, nasopharyngitis, pain in extremity, pyrexia, respiratory tract infection, and vomiting
- Adult patients with GHD: Adverse reactions reported in >2% of patients are: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral edema, vomiting, adrenal insufficiency, hypertension, blood creatine phosphokinase increase, weight increase, anemia
Drug Interactions
- Glucocorticoids: Patients treated with glucocorticoid for hypoadrenalism may require an increase in their maintenance or stress doses following initiation of Sogroya®
- Cytochrome P450-Metabolized Drugs: Sogroya® may alter the clearance. Monitor carefully if used with Sogroya®
- Oral Estrogen: Patients receiving oral estrogen replacement may require higher Sogroya® dosages
- Insulin and/or Other Antihyperglycemic Agents: Dose adjustment of insulin and/or antihyperglycemic agent may be required for patients with diabetes mellitus
Please click here for Sogroya® Prescribing Information.
Indications and Usage
Sogroya® (somapacitan-beco) injection 5 mg, 10 mg, or 15 mg is indicated for the:
- treatment of pediatric patients aged 2.5 years and older with:
- Growth failure due to inadequate secretion of endogenous growth hormone (GH)
- Short stature born Small for Gestational Age (SGA) and with no catch-up growth by 2 years of age
- Growth failure associated with Noonan Syndrome (NS)
- Idiopathic Short Stature (ISS)
- replacement of endogenous GH in adults with growth hormone deficiency (GHD)
Important Safety Information for Tresiba®
Contraindications
- Tresiba® is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin degludec or any of the excipients in Tresiba®
Warnings and Precautions
- Never Share a Tresiba® FlexTouch® Pen, Needle, or Syringe Between Patients, even if the needle is changed. Patients using Tresiba® vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
- Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, or injection site or method of administration) may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia. Make any changes to a patient’s insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. Adjustments in concomitant anti-diabetic treatment may be needed.
- Hypoglycemia: Hypoglycemia is the most common adverse reaction of insulin, including Tresiba®. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) or who experience recurrent hypoglycemia. The long-acting effect of Tresiba® may delay recovery from hypoglycemia compared to shorter-acting insulins.
Risk Factors for Hypoglycemia: The risk of hypoglycemia generally increases with intensity of glycemic control. The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of Tresiba® may vary among different patients or at different times in the same patients and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature. Other factors which may increase the risk of hypoglycemia include changes in meal pattern, changes in level of physical activity, or changes to concomitant drugs. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia. Patients and caregivers must be educated to recognize and manage hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended. - Hypoglycemia Due to Medication Errors: Accidental mix-ups between insulin products have been reported. To avoid medication errors between Tresiba® and other insulins, always instruct patients to always check the insulin label before each injection. To avoid dosing errors and potential overdose, never use a syringe to remove Tresiba® from the Tresiba® FlexTouch® disposable insulin prefilled pen.
- Hypersensitivity Reactions: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including Tresiba®. If hypersensitivity reactions occur, discontinue Tresiba®; treat per standard of care and monitor until symptoms and signs resolve.
- Hypokalemia: All insulins, including Tresiba®, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia and treat if indicated.
- Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention and heart failure can occur with concomitant use of thiazolidinediones (TZDs), which are PPAR-gamma agonists, and insulin, including Tresiba®. Patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of the TZD must be considered.
Adverse Reactions
- Adverse reactions commonly associated with Tresiba® are hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain.
Drug Interactions
- There are certain drugs that may cause clinically significant drug interactions with Tresiba®.
- Drugs that may increase the risk of hypoglycemia: antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors
- Drugs that may decrease the blood glucose lowering effect: atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones
- Drugs that may increase or decrease the blood glucose lowering effect: alcohol, beta-blockers, clonidine, lithium salts, and pentamidine
- Drugs that may blunt the signs and symptoms of hypoglycemia: beta-blockers, clonidine, guanethidine, and reserpine
Please click here for Tresiba® Prescribing Information.
Important Safety Information for Tretten®
Tretten® is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.
Tretten® may cause allergic reactions. If signs or symptoms of anaphylaxis or hypersensitivity reactions (including urticaria, rash, tightness of the chest, wheezing, hypotension) occur, discontinue immediately and institute appropriate treatment.
Thromboembolic complications may occur. Monitor patients with conditions that predispose to thrombosis for signs and symptoms of thrombosis after administration of Tretten®.
Inhibitory antibodies may occur with Tretten®. Patients with inhibitory antibodies may manifest as an inadequate response to treatment. If expected plasma FXIII activity levels are not attained, or if breakthrough bleeding occurs while receiving prophylaxis, perform an assay that measures FXIII inhibitory antibody concentrations.
The most common adverse reactions reported in clinical trials (≥1%) were headache, pain in the extremities, pain at injection site, and increase in fibrin D dimer levels.
Thrombosis may occur if Tretten® is administered concomitantly with Factor VIIa.
There are no adequate and well-controlled studies using Tretten® in pregnant women to determine whether there is a drug-associated risk. Animal reproduction studies have not been conducted with Tretten®.
Please click here for Tretten® Prescribing Information.